TY - JOUR
TI - RASSF1A promoter methylation in high-grade serous ovarian cancer: A direct comparison study in primary tumors, adjacent morphologically tumor cell-free tissues and paired circulating tumor DNA
AU - Giannopoulou, L.
AU - Chebouti, I.
AU - Pavlakis, K.
AU - Kasimir-Bauer, S.
AU - Lianidou, E.S.
JO - OncoTargets and therapy
PY - 2017
VL - 8
TODO - 13
SP - 21429-21443
PB - Impact Journals, LLC
SN - null
TODO - 10.18632/oncotarget.15249
TODO - platinum complex;  Ras association domain family protein 1A, adult;  Article;  cancer grading;  cancer growth;  cancer prognosis;  cancer survival;  cell free system;  circulating tumor cell;  controlled study;  distant metastasis;  DNA isolation;  DNA methylation;  female;  gene locus;  heterozygosity loss;  high grade serous ovarian cancer;  high resolution melting analysis;  human;  human tissue;  ovary cancer;  overall survival;  progression free survival;  promoter region;  protein methylation;  RASSF1A gene;  real time polymerase chain reaction;  tumor gene
TODO - The RASSF1A promoter is frequently methylated in high-grade serous ovarian cancer (HGSC). We examined RASSF1A promoter methylation in primary tumors, adjacent morphologically tumor cell-free tissues and corresponding circulating tumor DNA (ctDNA) samples of patients with HGSC, using a real-time methylation specific PCR (real-time MSP) and a methylation-sensitive high-resolution melting analysis (MS-HRMA) assay for the detection and semi-quantitative estimation of methylation, respectively. Two groups of primary HGSC tumor FFPE samples were recruited (Group A n=67 and Group B n=61), along with matched adjacent morphologically tumor cellfree tissues (n=58) and corresponding plasma samples (n=59) for group B. Using both assays, RASSF1A promoter was found highly methylated in primary tumors of both groups, and at lower percentages in the adjacent morphologically tumor cell-free tissues. Interestingly, RASSF1A promoter methylation was also observed in ctDNA by real-time MSP. Overall survival (OS) was significantly associated with RASSF1A promoter methylation in primary tumor samples using MS-HRMA (P=0.023). Our results clearly indicate that RASSF1A promoter is methylated in adjacent tissue surrounding the tumor in HGSC patients. We report for the first time that RASSF1A promoter methylation provides significant prognostic information in HGSC patients.
ER -